CA2139442A1 - Heterocyclic compounds as pharmaceutical - Google Patents

Heterocyclic compounds as pharmaceutical

Info

Publication number: CA2139442A1
Authority: CA; Canada
Prior art keywords: formula; group; compound; pharmaceutically acceptable; moiety
Prior art date: 1992-07-03
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Abandoned

Application number

CA002139442A

Other languages

English (en)

French (fr)

Inventor

David Haigh

John T. Sime

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

SmithKline Beecham Ltd

Original Assignee

Individual

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1992-07-03

Filing date

1993-06-29

Publication date

1994-01-20

1992-07-03 Priority claimed from GB929214185A external-priority patent/GB9214185D0/en

1992-12-29 Priority claimed from GB929227030A external-priority patent/GB9227030D0/en

1993-05-28 Priority claimed from GB939311027A external-priority patent/GB9311027D0/en

1993-06-29 Application filed by Individual filed Critical Individual

1994-01-20 Publication of CA2139442A1 publication Critical patent/CA2139442A1/en

Status Abandoned legal-status Critical Current

Links

150000002391 heterocyclic compounds Chemical class 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 146
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 101
125000003118 aryl group Chemical group 0.000 claims abstract description 65
150000003839 salts Chemical class 0.000 claims abstract description 62
125000000217 alkyl group Chemical group 0.000 claims abstract description 49
239000012453 solvate Substances 0.000 claims abstract description 41
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 31
239000001257 hydrogen Substances 0.000 claims abstract description 29
125000000623 heterocyclic group Chemical group 0.000 claims abstract description 23
125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 19
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 19
229910052757 nitrogen Inorganic materials 0.000 claims abstract description 17
125000002252 acyl group Chemical group 0.000 claims abstract description 8
125000004448 alkyl carbonyl group Chemical group 0.000 claims abstract description 7
238000004519 manufacturing process Methods 0.000 claims abstract description 5
125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 5
229910002091 carbon monoxide Inorganic materials 0.000 claims abstract description 4
125000001424 substituent group Chemical group 0.000 claims abstract description 4
239000003814 drug Substances 0.000 claims abstract 3
238000000034 method Methods 0.000 claims description 74
238000006243 chemical reaction Methods 0.000 claims description 61
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 52
-1 alyl Chemical group 0.000 claims description 31
239000002253 acid Substances 0.000 claims description 27
239000003153 chemical reaction reagent Substances 0.000 claims description 27
229910052799 carbon Inorganic materials 0.000 claims description 20
238000011321 prophylaxis Methods 0.000 claims description 17
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 13
125000003545 alkoxy group Chemical group 0.000 claims description 13
150000002148 esters Chemical class 0.000 claims description 12
125000006239 protecting group Chemical group 0.000 claims description 11
108090001060 Lipase Proteins 0.000 claims description 10
239000004367 Lipase Substances 0.000 claims description 10
102000004882 Lipase Human genes 0.000 claims description 10
125000004432 carbon atom Chemical group C* 0.000 claims description 10
235000019421 lipase Nutrition 0.000 claims description 10
238000002360 preparation method Methods 0.000 claims description 10
238000011282 treatment Methods 0.000 claims description 10
208000030814 Eating disease Diseases 0.000 claims description 8
208000019454 Feeding and Eating disease Diseases 0.000 claims description 8
PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 claims description 8
235000014632 disordered eating Nutrition 0.000 claims description 8
HZVOZRGWRWCICA-UHFFFAOYSA-N methanediyl Chemical compound [CH2] HZVOZRGWRWCICA-UHFFFAOYSA-N 0.000 claims description 8
229910052760 oxygen Inorganic materials 0.000 claims description 8
239000000758 substrate Substances 0.000 claims description 8
208000024172 Cardiovascular disease Diseases 0.000 claims description 7
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 6
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
125000005843 halogen group Chemical group 0.000 claims description 6
230000003301 hydrolyzing effect Effects 0.000 claims description 6
125000004400 (C1-C12) alkyl group Chemical group 0.000 claims description 5
206010020772 Hypertension Diseases 0.000 claims description 5
150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 5
125000004185 ester group Chemical group 0.000 claims description 5
150000004820 halides Chemical class 0.000 claims description 5
241000235527 Rhizopus Species 0.000 claims description 4
241000303962 Rhizopus delemar Species 0.000 claims description 4
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 4
239000005864 Sulphur Chemical group 0.000 claims description 4
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 4
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
230000003345 hyperglycaemic effect Effects 0.000 claims description 4
201000001421 hyperglycemia Diseases 0.000 claims description 4
231100000252 nontoxic Toxicity 0.000 claims description 4
230000003000 nontoxic effect Effects 0.000 claims description 4
230000003287 optical effect Effects 0.000 claims description 4
239000001301 oxygen Substances 0.000 claims description 4
229910052783 alkali metal Inorganic materials 0.000 claims description 3
125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 3
125000004429 atom Chemical group 0.000 claims description 3
125000003831 tetrazolyl group Chemical group 0.000 claims description 3
241000235403 Rhizomucor miehei Species 0.000 claims description 2
230000002140 halogenating effect Effects 0.000 claims description 2
239000000126 substance Substances 0.000 claims description 2
208000031226 Hyperlipidaemia Diseases 0.000 claims 3
240000005384 Rhizopus oryzae Species 0.000 claims 1
235000013752 Rhizopus oryzae Nutrition 0.000 claims 1
230000002152 alkylating effect Effects 0.000 claims 1
239000003937 drug carrier Substances 0.000 claims 1
239000008194 pharmaceutical composition Substances 0.000 claims 1
230000001225 therapeutic effect Effects 0.000 claims 1
239000000203 mixture Substances 0.000 abstract description 21
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 135
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 110
238000005481 NMR spectroscopy Methods 0.000 description 77
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 66
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 60
239000000243 solution Substances 0.000 description 56
229940093499 ethyl acetate Drugs 0.000 description 45
235000019439 ethyl acetate Nutrition 0.000 description 45
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 45
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 31
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 31
239000002904 solvent Substances 0.000 description 27
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 26
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
VLKZOEOYAKHREP-UHFFFAOYSA-N hexane Substances CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 23
229910052943 magnesium sulfate Inorganic materials 0.000 description 23
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 22
239000000741 silica gel Substances 0.000 description 21
229910002027 silica gel Inorganic materials 0.000 description 21
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 18
239000012267 brine Substances 0.000 description 17
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 17
XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical compound CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 16
239000000047 product Substances 0.000 description 16
239000003921 oil Substances 0.000 description 15
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 14
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 14
239000003480 eluent Substances 0.000 description 14
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 14
238000010992 reflux Methods 0.000 description 14
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 13
235000019341 magnesium sulphate Nutrition 0.000 description 13
239000012312 sodium hydride Substances 0.000 description 13
229910000104 sodium hydride Inorganic materials 0.000 description 13
239000007787 solid Substances 0.000 description 13
SPEUIVXLLWOEMJ-UHFFFAOYSA-N 1,1-dimethoxyethane Chemical compound COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 12
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 11
239000002585 base Substances 0.000 description 10
230000015572 biosynthetic process Effects 0.000 description 10
239000000460 chlorine Substances 0.000 description 10
150000002500 ions Chemical class 0.000 description 10
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
229910052736 halogen Inorganic materials 0.000 description 9
150000002367 halogens Chemical class 0.000 description 9
KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 8
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 8
230000037213 diet Effects 0.000 description 8
235000005911 diet Nutrition 0.000 description 8
239000006185 dispersion Substances 0.000 description 8
230000009467 reduction Effects 0.000 description 8
238000006722 reduction reaction Methods 0.000 description 8
239000000010 aprotic solvent Substances 0.000 description 7
238000000605 extraction Methods 0.000 description 7
239000008103 glucose Substances 0.000 description 7
230000007062 hydrolysis Effects 0.000 description 7
238000006460 hydrolysis reaction Methods 0.000 description 7
125000002887 hydroxy group Chemical group [H]O* 0.000 description 7
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 7
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 6
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 6
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 6
239000003795 chemical substances by application Substances 0.000 description 6
MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 6
239000012299 nitrogen atmosphere Substances 0.000 description 6
238000000746 purification Methods 0.000 description 6
239000011734 sodium Substances 0.000 description 6
238000003756 stirring Methods 0.000 description 6
PPKPKFIWDXDAGC-IHWYPQMZSA-N (z)-1,2-dichloroprop-1-ene Chemical compound C\C(Cl)=C\Cl PPKPKFIWDXDAGC-IHWYPQMZSA-N 0.000 description 5
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 5
229960000583 acetic acid Drugs 0.000 description 5
125000003943 azolyl group Chemical group 0.000 description 5
150000001721 carbon Chemical group 0.000 description 5
229910052751 metal Inorganic materials 0.000 description 5
239000002184 metal Substances 0.000 description 5
125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 5
239000002480 mineral oil Substances 0.000 description 5
235000010446 mineral oil Nutrition 0.000 description 5
239000012074 organic phase Substances 0.000 description 5
125000006413 ring segment Chemical group 0.000 description 5
229910052708 sodium Inorganic materials 0.000 description 5
102000004190 Enzymes Human genes 0.000 description 4
108090000790 Enzymes Proteins 0.000 description 4
WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 4
241000699670 Mus sp. Species 0.000 description 4
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
239000008280 blood Substances 0.000 description 4
210000004369 blood Anatomy 0.000 description 4
238000007796 conventional method Methods 0.000 description 4
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
239000000284 extract Substances 0.000 description 4
125000005842 heteroatom Chemical group 0.000 description 4
238000004128 high performance liquid chromatography Methods 0.000 description 4
ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 4
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
159000000000 sodium salts Chemical class 0.000 description 4
239000000725 suspension Substances 0.000 description 4
BBVIDBNAYOIXOE-UHFFFAOYSA-N 1,2,4-oxadiazole Chemical compound C=1N=CON=1 BBVIDBNAYOIXOE-UHFFFAOYSA-N 0.000 description 3
OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 3
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 3
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 3
DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 3
239000004480 active ingredient Substances 0.000 description 3
239000011942 biocatalyst Substances 0.000 description 3
229910052801 chlorine Inorganic materials 0.000 description 3
125000001309 chloro group Chemical group Cl* 0.000 description 3
238000005859 coupling reaction Methods 0.000 description 3
239000008367 deionised water Substances 0.000 description 3
238000010828 elution Methods 0.000 description 3
125000001153 fluoro group Chemical group F* 0.000 description 3
239000006260 foam Substances 0.000 description 3
229910052744 lithium Inorganic materials 0.000 description 3
230000000707 stereoselective effect Effects 0.000 description 3
229910052717 sulfur Inorganic materials 0.000 description 3
229910021653 sulphate ion Inorganic materials 0.000 description 3
NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 2
125000006273 (C1-C3) alkyl group Chemical group 0.000 description 2
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 description 2
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
BSFODEXXVBBYOC-UHFFFAOYSA-N 8-[4-(dimethylamino)butan-2-ylamino]quinolin-6-ol Chemical compound C1=CN=C2C(NC(CCN(C)C)C)=CC(O)=CC2=C1 BSFODEXXVBBYOC-UHFFFAOYSA-N 0.000 description 2
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
208000000103 Anorexia Nervosa Diseases 0.000 description 2
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
208000032841 Bulimia Diseases 0.000 description 2
206010006550 Bulimia nervosa Diseases 0.000 description 2
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 2
HSRJKNPTNIJEKV-UHFFFAOYSA-N Guaifenesin Chemical compound COC1=CC=CC=C1OCC(O)CO HSRJKNPTNIJEKV-UHFFFAOYSA-N 0.000 description 2
238000010268 HPLC based assay Methods 0.000 description 2
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
206010020710 Hyperphagia Diseases 0.000 description 2
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
208000008589 Obesity Diseases 0.000 description 2
241000183024 Populus tremula Species 0.000 description 2
LOUPRKONTZGTKE-WZBLMQSHSA-N Quinine Chemical compound C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-WZBLMQSHSA-N 0.000 description 2
SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
125000000129 anionic group Chemical group 0.000 description 2
239000008346 aqueous phase Substances 0.000 description 2
AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 2
125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 2
ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 2
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
239000003054 catalyst Substances 0.000 description 2
238000010531 catalytic reduction reaction Methods 0.000 description 2
239000003638 chemical reducing agent Substances 0.000 description 2
XTEGARKTQYYJKE-UHFFFAOYSA-N chloric acid Chemical compound OCl(=O)=O XTEGARKTQYYJKE-UHFFFAOYSA-N 0.000 description 2
229940005991 chloric acid Drugs 0.000 description 2
238000004587 chromatography analysis Methods 0.000 description 2
239000007822 coupling agent Substances 0.000 description 2
125000004122 cyclic group Chemical group 0.000 description 2
238000010790 dilution Methods 0.000 description 2
239000012895 dilution Substances 0.000 description 2
229960001760 dimethyl sulfoxide Drugs 0.000 description 2
208000035475 disorder Diseases 0.000 description 2
239000002552 dosage form Substances 0.000 description 2
238000005886 esterification reaction Methods 0.000 description 2
238000001704 evaporation Methods 0.000 description 2
230000008020 evaporation Effects 0.000 description 2
230000037406 food intake Effects 0.000 description 2
235000012631 food intake Nutrition 0.000 description 2
IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 2
150000004678 hydrides Chemical class 0.000 description 2
XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 2
239000012442 inert solvent Substances 0.000 description 2
229910052740 iodine Inorganic materials 0.000 description 2
239000011630 iodine Substances 0.000 description 2
OWFXIOWLTKNBAP-UHFFFAOYSA-N isoamyl nitrite Chemical compound CC(C)CCON=O OWFXIOWLTKNBAP-UHFFFAOYSA-N 0.000 description 2
238000002955 isolation Methods 0.000 description 2
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
CFHGBZLNZZVTAY-UHFFFAOYSA-N lawesson's reagent Chemical compound C1=CC(OC)=CC=C1P1(=S)SP(=S)(C=2C=CC(OC)=CC=2)S1 CFHGBZLNZZVTAY-UHFFFAOYSA-N 0.000 description 2
239000000463 material Substances 0.000 description 2
229910052987 metal hydride Inorganic materials 0.000 description 2
150000004681 metal hydrides Chemical class 0.000 description 2
VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
125000002950 monocyclic group Chemical group 0.000 description 2
DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 description 2
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
125000001624 naphthyl group Chemical group 0.000 description 2
235000020824 obesity Nutrition 0.000 description 2
235000020830 overeating Nutrition 0.000 description 2
125000002971 oxazolyl group Chemical group 0.000 description 2
125000003884 phenylalkyl group Chemical group 0.000 description 2
125000001476 phosphono group Chemical group [H]OP(*)(=O)O[H] 0.000 description 2
XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
239000000843 powder Substances 0.000 description 2
235000019260 propionic acid Nutrition 0.000 description 2
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
239000011541 reaction mixture Substances 0.000 description 2
YNWSXIWHOSSPCO-UHFFFAOYSA-N rhodium(2+) Chemical class [Rh+2] YNWSXIWHOSSPCO-UHFFFAOYSA-N 0.000 description 2
ITDJKCJYYAQMRO-UHFFFAOYSA-L rhodium(2+);diacetate Chemical compound [Rh+2].CC([O-])=O.CC([O-])=O ITDJKCJYYAQMRO-UHFFFAOYSA-L 0.000 description 2
VUPQHSHTKBZVML-UHFFFAOYSA-J rhodium(3+);tetraacetate Chemical compound [Rh+3].[Rh+3].CC([O-])=O.CC([O-])=O.CC([O-])=O.CC([O-])=O VUPQHSHTKBZVML-UHFFFAOYSA-J 0.000 description 2
229910052701 rubidium Inorganic materials 0.000 description 2
150000003385 sodium Chemical class 0.000 description 2
HJHVQCXHVMGZNC-JCJNLNMISA-M sodium;(2z)-2-[(3r,4s,5s,8s,9s,10s,11r,13r,14s,16s)-16-acetyloxy-3,11-dihydroxy-4,8,10,14-tetramethyl-2,3,4,5,6,7,9,11,12,13,15,16-dodecahydro-1h-cyclopenta[a]phenanthren-17-ylidene]-6-methylhept-5-enoate Chemical compound [Na+].O[C@@H]([C@@H]12)C[C@H]3\C(=C(/CCC=C(C)C)C([O-])=O)[C@@H](OC(C)=O)C[C@]3(C)[C@@]2(C)CC[C@@H]2[C@]1(C)CC[C@@H](O)[C@H]2C HJHVQCXHVMGZNC-JCJNLNMISA-M 0.000 description 2
108010079522 solysime Proteins 0.000 description 2
UDYFLDICVHJSOY-UHFFFAOYSA-N sulfur trioxide pyridine complex Chemical compound O=S(=O)=O.C1=CC=NC=C1 UDYFLDICVHJSOY-UHFFFAOYSA-N 0.000 description 2
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
238000012360 testing method Methods 0.000 description 2
LEIMLDGFXIOXMT-UHFFFAOYSA-N trimethylsilyl cyanide Chemical compound C[Si](C)(C)C#N LEIMLDGFXIOXMT-UHFFFAOYSA-N 0.000 description 2
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
238000005406 washing Methods 0.000 description 2
229910052727 yttrium Inorganic materials 0.000 description 2
125000006274 (C1-C3)alkoxy group Chemical group 0.000 description 1
125000004169 (C1-C6) alkyl group Chemical group 0.000 description 1
125000006701 (C1-C7) alkyl group Chemical group 0.000 description 1
125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 description 1
125000001140 1,4-phenylene group Chemical group [H]C1=C([H])C([*:2])=C([H])C([H])=C1[*:1] 0.000 description 1
SHCFCJUJGBRSPO-UHFFFAOYSA-N 1-cyclohexylcyclohexan-1-amine Chemical compound C1CCCCC1C1(N)CCCCC1 SHCFCJUJGBRSPO-UHFFFAOYSA-N 0.000 description 1
238000005160 1H NMR spectroscopy Methods 0.000 description 1
SVPKNMBRVBMTLB-UHFFFAOYSA-N 2,3-dichloronaphthalene-1,4-dione Chemical compound C1=CC=C2C(=O)C(Cl)=C(Cl)C(=O)C2=C1 SVPKNMBRVBMTLB-UHFFFAOYSA-N 0.000 description 1
KZDCMKVLEYCGQX-UDPGNSCCSA-N 2-(diethylamino)ethyl 4-aminobenzoate;(2s,5r,6r)-3,3-dimethyl-7-oxo-6-[(2-phenylacetyl)amino]-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid;hydrate Chemical compound O.CCN(CC)CCOC(=O)C1=CC=C(N)C=C1.N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 KZDCMKVLEYCGQX-UDPGNSCCSA-N 0.000 description 1
HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 1
LITDWGSWBCBPDI-UHFFFAOYSA-N 2-[1,3-benzoxazol-2-yl(methyl)amino]ethanol Chemical compound C1=CC=C2OC(N(CCO)C)=NC2=C1 LITDWGSWBCBPDI-UHFFFAOYSA-N 0.000 description 1
UGIYZSSCRPGTIE-UHFFFAOYSA-N 2-[4-[2-[1,3-benzoxazol-2-yl(methyl)amino]ethoxy]phenyl]ethanol Chemical compound N=1C2=CC=CC=C2OC=1N(C)CCOC1=CC=C(CCO)C=C1 UGIYZSSCRPGTIE-UHFFFAOYSA-N 0.000 description 1
VWROGAJAHBGEKL-UHFFFAOYSA-N 2-[hydroxy(phenylperoxy)phosphoryl]acetic acid Chemical compound OC(=O)CP(O)(=O)OOC1=CC=CC=C1 VWROGAJAHBGEKL-UHFFFAOYSA-N 0.000 description 1
KSIFOIXRKPNHLO-UHFFFAOYSA-N 2-ethoxypropanamide Chemical compound CCOC(C)C(N)=O KSIFOIXRKPNHLO-UHFFFAOYSA-N 0.000 description 1
HSHGWTBQFJUYOD-UHFFFAOYSA-N 2-methoxy-3-[4-[2-[methyl(pyridin-2-yl)amino]ethoxy]phenyl]propanenitrile Chemical compound C1=CC(CC(OC)C#N)=CC=C1OCCN(C)C1=CC=CC=N1 HSHGWTBQFJUYOD-UHFFFAOYSA-N 0.000 description 1
MWDCBSZUHUONCE-UHFFFAOYSA-N 2-propan-2-yloxypropanoic acid Chemical compound CC(C)OC(C)C(O)=O MWDCBSZUHUONCE-UHFFFAOYSA-N 0.000 description 1
WGTASENVNYJZBK-UHFFFAOYSA-N 3,4,5-trimethoxyamphetamine Chemical compound COC1=CC(CC(C)N)=CC(OC)=C1OC WGTASENVNYJZBK-UHFFFAOYSA-N 0.000 description 1
MVNGEUAUNZSXLM-UHFFFAOYSA-N 3-[4-[2-[1,3-benzoxazol-2-yl(methyl)amino]ethoxy]phenyl]-2-phenylmethoxypropanoic acid Chemical compound N=1C2=CC=CC=C2OC=1N(C)CCOC(C=C1)=CC=C1CC(C(O)=O)OCC1=CC=CC=C1 MVNGEUAUNZSXLM-UHFFFAOYSA-N 0.000 description 1
IYTJRMRETHPZAC-UHFFFAOYSA-N 4,4-dibenzylpiperidine Chemical compound C1CNCCC1(CC=1C=CC=CC=1)CC1=CC=CC=C1 IYTJRMRETHPZAC-UHFFFAOYSA-N 0.000 description 1
JDIPHBYZUMQFQV-UHFFFAOYSA-N 5-ethyl-1h-1,2,4-triazole Chemical compound CCC1=NC=NN1 JDIPHBYZUMQFQV-UHFFFAOYSA-N 0.000 description 1
JRLTTZUODKEYDH-UHFFFAOYSA-N 8-methylquinoline Chemical group C1=CN=C2C(C)=CC=CC2=C1 JRLTTZUODKEYDH-UHFFFAOYSA-N 0.000 description 1
201000001320 Atherosclerosis Diseases 0.000 description 1
BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 description 1
101150048931 COY1 gene Proteins 0.000 description 1
241000282472 Canis lupus familiaris Species 0.000 description 1
KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
235000001258 Cinchona calisaya Nutrition 0.000 description 1
KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 1
NPOJQCVWMSKXDN-UHFFFAOYSA-N Dacthal Chemical compound COC(=O)C1=C(Cl)C(Cl)=C(C(=O)OC)C(Cl)=C1Cl NPOJQCVWMSKXDN-UHFFFAOYSA-N 0.000 description 1
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
101100353161 Drosophila melanogaster prel gene Proteins 0.000 description 1
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
229920000168 Microcrystalline cellulose Polymers 0.000 description 1
244000294411 Mirabilis expansa Species 0.000 description 1
235000015429 Mirabilis expansa Nutrition 0.000 description 1
YFONKFDEZLYQDH-OPQQBVKSSA-N N-[(1R,2S)-2,6-dimethyindan-1-yl]-6-[(1R)-1-fluoroethyl]-1,3,5-triazine-2,4-diamine Chemical compound C[C@@H](F)C1=NC(N)=NC(N[C@H]2C3=CC(C)=CC=C3C[C@@H]2C)=N1 YFONKFDEZLYQDH-OPQQBVKSSA-N 0.000 description 1
MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
229910002651 NO3 Inorganic materials 0.000 description 1
NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
IOVCWXUNBOPUCH-UHFFFAOYSA-M Nitrite anion Chemical compound [O-]N=O IOVCWXUNBOPUCH-UHFFFAOYSA-M 0.000 description 1
229910019142 PO4 Inorganic materials 0.000 description 1
229910019213 POCl3 Inorganic materials 0.000 description 1
241000282320 Panthera leo Species 0.000 description 1
YNPNZTXNASCQKK-UHFFFAOYSA-N Phenanthrene Natural products C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 description 1
235000014328 Schoenoplectus acutus var occidentalis Nutrition 0.000 description 1
244000136421 Scirpus acutus Species 0.000 description 1
235000014326 Scirpus californicus Nutrition 0.000 description 1
235000017913 Scirpus lacustris Nutrition 0.000 description 1
DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
239000004141 Sodium laurylsulphate Substances 0.000 description 1
229920002472 Starch Polymers 0.000 description 1
241000269838 Thunnus thynnus Species 0.000 description 1
GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
RHQDFWAXVIIEBN-UHFFFAOYSA-N Trifluoroethanol Chemical compound OCC(F)(F)F RHQDFWAXVIIEBN-UHFFFAOYSA-N 0.000 description 1
238000007239 Wittig reaction Methods 0.000 description 1
JVVXZOOGOGPDRZ-SLFFLAALSA-N [(1R,4aS,10aR)-1,4a-dimethyl-7-propan-2-yl-2,3,4,9,10,10a-hexahydrophenanthren-1-yl]methanamine Chemical compound NC[C@]1(C)CCC[C@]2(C)C3=CC=C(C(C)C)C=C3CC[C@H]21 JVVXZOOGOGPDRZ-SLFFLAALSA-N 0.000 description 1
238000010521 absorption reaction Methods 0.000 description 1
150000001241 acetals Chemical class 0.000 description 1
150000001242 acetic acid derivatives Chemical class 0.000 description 1
DRGVLUZIGUIMLB-UHFFFAOYSA-N acetic acid;rhodium Chemical compound [Rh].[Rh].CC(O)=O.CC(O)=O.CC(O)=O.CC(O)=O DRGVLUZIGUIMLB-UHFFFAOYSA-N 0.000 description 1
230000002378 acidificating effect Effects 0.000 description 1
230000003213 activating effect Effects 0.000 description 1
230000010933 acylation Effects 0.000 description 1
238000005917 acylation reaction Methods 0.000 description 1
239000002671 adjuvant Substances 0.000 description 1
125000005236 alkanoylamino group Chemical group 0.000 description 1
125000003342 alkenyl group Chemical group 0.000 description 1
125000005907 alkyl ester group Chemical group 0.000 description 1
230000029936 alkylation Effects 0.000 description 1
238000005804 alkylation reaction Methods 0.000 description 1
238000004458 analytical method Methods 0.000 description 1
150000008064 anhydrides Chemical class 0.000 description 1
HOPRXXXSABQWAV-UHFFFAOYSA-N anhydrous collidine Natural products CC1=CC=NC(C)=C1C HOPRXXXSABQWAV-UHFFFAOYSA-N 0.000 description 1
208000022531 anorexia Diseases 0.000 description 1
230000036528 appetite Effects 0.000 description 1
235000019789 appetite Nutrition 0.000 description 1
239000006286 aqueous extract Substances 0.000 description 1
239000003125 aqueous solvent Substances 0.000 description 1
229910052786 argon Inorganic materials 0.000 description 1
238000003556 assay Methods 0.000 description 1
239000012298 atmosphere Substances 0.000 description 1
238000009835 boiling Methods 0.000 description 1
UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 1
229910010277 boron hydride Inorganic materials 0.000 description 1
239000000872 buffer Substances 0.000 description 1
244000309464 bull Species 0.000 description 1
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
239000002775 capsule Substances 0.000 description 1
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 1
239000000969 carrier Substances 0.000 description 1
238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
125000002091 cationic group Chemical group 0.000 description 1
238000004296 chiral HPLC Methods 0.000 description 1
LOUPRKONTZGTKE-UHFFFAOYSA-N cinchonine Natural products C1C(C(C2)C=C)CCN2C1C(O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-UHFFFAOYSA-N 0.000 description 1
UTBIMNXEDGNJFE-UHFFFAOYSA-N collidine Natural products CC1=CC=C(C)C(C)=N1 UTBIMNXEDGNJFE-UHFFFAOYSA-N 0.000 description 1
238000001816 cooling Methods 0.000 description 1
230000008878 coupling Effects 0.000 description 1
238000010168 coupling process Methods 0.000 description 1
239000013078 crystal Substances 0.000 description 1
238000012258 culturing Methods 0.000 description 1
125000000753 cycloalkyl group Chemical group 0.000 description 1
206010061428 decreased appetite Diseases 0.000 description 1
238000005661 deetherification reaction Methods 0.000 description 1
125000003963 dichloro group Chemical group Cl* 0.000 description 1
ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 1
125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
229940079919 digestives enzyme preparation Drugs 0.000 description 1
239000003085 diluting agent Substances 0.000 description 1
125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
238000001035 drying Methods 0.000 description 1
230000000694 effects Effects 0.000 description 1
229940088598 enzyme Drugs 0.000 description 1
238000010931 ester hydrolysis Methods 0.000 description 1
230000032050 esterification Effects 0.000 description 1
SFTYDROGLAWTKI-UHFFFAOYSA-N ethyl 3-(4-hydroxyphenyl)-2-methoxypropanoate Chemical compound CCOC(=O)C(OC)CC1=CC=C(O)C=C1 SFTYDROGLAWTKI-UHFFFAOYSA-N 0.000 description 1
FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 1
238000002474 experimental method Methods 0.000 description 1
239000000945 filler Substances 0.000 description 1
239000000706 filtrate Substances 0.000 description 1
238000001914 filtration Methods 0.000 description 1
239000000796 flavoring agent Substances 0.000 description 1
239000011737 fluorine Substances 0.000 description 1
229910052731 fluorine Inorganic materials 0.000 description 1
125000003709 fluoroalkyl group Chemical group 0.000 description 1
239000007789 gas Substances 0.000 description 1
239000012362 glacial acetic acid Substances 0.000 description 1
230000005484 gravity Effects 0.000 description 1
125000001188 haloalkyl group Chemical group 0.000 description 1
125000001475 halogen functional group Chemical group 0.000 description 1
230000026030 halogenation Effects 0.000 description 1
238000005658 halogenation reaction Methods 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
150000004677 hydrates Chemical class 0.000 description 1
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
125000002768 hydroxyalkyl group Chemical group 0.000 description 1
125000004464 hydroxyphenyl group Chemical group 0.000 description 1
230000000055 hyoplipidemic effect Effects 0.000 description 1
230000003516 hyperlipidaemic effect Effects 0.000 description 1
239000004615 ingredient Substances 0.000 description 1
238000002347 injection Methods 0.000 description 1
239000007924 injection Substances 0.000 description 1
230000010354 integration Effects 0.000 description 1
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
239000011968 lewis acid catalyst Substances 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
238000001819 mass spectrum Methods 0.000 description 1
SJFNDMHZXCUXSA-UHFFFAOYSA-M methoxymethyl(triphenyl)phosphanium;chloride Chemical compound [Cl-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(COC)C1=CC=CC=C1 SJFNDMHZXCUXSA-UHFFFAOYSA-M 0.000 description 1
KUCRTUQUAYLJDC-UHFFFAOYSA-N methyl 2-(2-methoxy-2-oxoethoxy)acetate Chemical compound COC(=O)COCC(=O)OC KUCRTUQUAYLJDC-UHFFFAOYSA-N 0.000 description 1
XGDZEDRBLVIUMX-UHFFFAOYSA-N methyl 2-(4-hydroxyphenyl)acetate Chemical compound COC(=O)CC1=CC=C(O)C=C1 XGDZEDRBLVIUMX-UHFFFAOYSA-N 0.000 description 1
SRNRRGDVQQJQLP-UHFFFAOYSA-N methyl 2-diazo-3-(4-hydroxyphenyl)propanoate Chemical compound COC(=O)C(=[N+]=[N-])CC1=CC=C(O)C=C1 SRNRRGDVQQJQLP-UHFFFAOYSA-N 0.000 description 1
PDFUCDWETSQSSU-UHFFFAOYSA-N methyl 2-hydroxy-3-(4-hydroxyphenyl)propanoate Chemical compound COC(=O)C(O)CC1=CC=C(O)C=C1 PDFUCDWETSQSSU-UHFFFAOYSA-N 0.000 description 1
NJNAFYWYGASZPM-UHFFFAOYSA-N methyl 3-(4-hydroxyphenyl)-2-(2,2,2-trifluoroethoxy)propanoate Chemical compound FC(F)(F)COC(C(=O)OC)CC1=CC=C(O)C=C1 NJNAFYWYGASZPM-UHFFFAOYSA-N 0.000 description 1
DRDPVLHCRHQIKR-UHFFFAOYSA-N methyl 3-(4-hydroxyphenyl)-2-methoxypropanoate Chemical compound COC(=O)C(OC)CC1=CC=C(O)C=C1 DRDPVLHCRHQIKR-UHFFFAOYSA-N 0.000 description 1
VPCZLFRNLCREEF-UHFFFAOYSA-N methyl 3-(4-hydroxyphenyl)-2-propoxypropanoate Chemical compound CCCOC(C(=O)OC)CC1=CC=C(O)C=C1 VPCZLFRNLCREEF-UHFFFAOYSA-N 0.000 description 1
KMNLLFDNNVDQOA-UHFFFAOYSA-N methyl 3-[4-[2-[1,3-benzoxazol-2-yl(methyl)amino]ethoxy]phenyl]-2-methoxypropanoate Chemical compound C1=CC(CC(OC)C(=O)OC)=CC=C1OCCN(C)C1=NC2=CC=CC=C2O1 KMNLLFDNNVDQOA-UHFFFAOYSA-N 0.000 description 1
MJIAMXSVBXRGLO-UHFFFAOYSA-N methyl 3-[4-[2-[1,3-benzoxazol-2-yl(methyl)amino]ethoxy]phenyl]-2-phenylmethoxypropanoate Chemical compound C=1C=C(OCCN(C)C=2OC3=CC=CC=C3N=2)C=CC=1CC(C(=O)OC)OCC1=CC=CC=C1 MJIAMXSVBXRGLO-UHFFFAOYSA-N 0.000 description 1
PDFUCDWETSQSSU-SECBINFHSA-N methyl 4-hydroxyphenyllactate Natural products COC(=O)[C@H](O)CC1=CC=C(O)C=C1 PDFUCDWETSQSSU-SECBINFHSA-N 0.000 description 1
MWZPENIJLUWBSY-VIFPVBQESA-N methyl L-tyrosinate Chemical compound COC(=O)[C@@H](N)CC1=CC=C(O)C=C1 MWZPENIJLUWBSY-VIFPVBQESA-N 0.000 description 1
150000004702 methyl esters Chemical class 0.000 description 1
235000019813 microcrystalline cellulose Nutrition 0.000 description 1
239000008108 microcrystalline cellulose Substances 0.000 description 1
229940016286 microcrystalline cellulose Drugs 0.000 description 1
235000013536 miso Nutrition 0.000 description 1
XONPDZSGENTBNJ-UHFFFAOYSA-N molecular hydrogen;sodium Chemical compound [Na].[H][H] XONPDZSGENTBNJ-UHFFFAOYSA-N 0.000 description 1
150000004682 monohydrates Chemical class 0.000 description 1
229910000403 monosodium phosphate Inorganic materials 0.000 description 1
235000019799 monosodium phosphate Nutrition 0.000 description 1
SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
238000010641 nitrile hydrolysis reaction Methods 0.000 description 1
238000013116 obese mouse model Methods 0.000 description 1
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
229940099990 ogen Drugs 0.000 description 1
238000007410 oral glucose tolerance test Methods 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
150000002894 organic compounds Chemical class 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
239000012071 phase Substances 0.000 description 1
125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 description 1
125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
239000010452 phosphate Substances 0.000 description 1
239000001253 polyvinylpolypyrrolidone Substances 0.000 description 1
235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 1
229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 1
239000001267 polyvinylpyrrolidone Substances 0.000 description 1
229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
150000003138 primary alcohols Chemical class 0.000 description 1
MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
229960004919 procaine Drugs 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
125000004076 pyridyl group Chemical group 0.000 description 1
125000000714 pyrimidinyl group Chemical group 0.000 description 1
229960000948 quinine Drugs 0.000 description 1
JWEQRJSCTFBRSI-PCLIKHOPSA-N rboxylate Chemical compound COC(=O)C1C(N2C3=O)C4=CC=CC=C4OC1(C)N=C2S\C3=C\C(C=1)=CC=C(OC)C=1COC1=CC=CC=C1C JWEQRJSCTFBRSI-PCLIKHOPSA-N 0.000 description 1
238000009938 salting Methods 0.000 description 1
AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
235000019333 sodium laurylsulphate Nutrition 0.000 description 1
229940080313 sodium starch Drugs 0.000 description 1
OJENKXNXJPNEPU-UHFFFAOYSA-N sodium;2-[4-(7-chloroquinoxalin-2-yl)oxyphenoxy]propanoic acid Chemical compound [Na+].C1=CC(OC(C)C(O)=O)=CC=C1OC1=CN=C(C=CC(Cl)=C2)C2=N1 OJENKXNXJPNEPU-UHFFFAOYSA-N 0.000 description 1
229940032147 starch Drugs 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
239000008107 starch Substances 0.000 description 1
239000012258 stirred mixture Substances 0.000 description 1
125000000547 substituted alkyl group Chemical group 0.000 description 1
YOEWQQVKRJEPAE-UHFFFAOYSA-L succinylcholine chloride (anhydrous) Chemical compound [Cl-].[Cl-].C[N+](C)(C)CCOC(=O)CCC(=O)OCC[N+](C)(C)C YOEWQQVKRJEPAE-UHFFFAOYSA-L 0.000 description 1
GFYHSKONPJXCDE-UHFFFAOYSA-N sym-collidine Natural products CC1=CN=C(C)C(C)=C1 GFYHSKONPJXCDE-UHFFFAOYSA-N 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
229940095064 tartrate Drugs 0.000 description 1
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
125000000335 thiazolyl group Chemical group 0.000 description 1
125000004055 thiomethyl group Chemical group [H]SC([H])([H])* 0.000 description 1
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
230000002110 toxicologic effect Effects 0.000 description 1
231100000759 toxicological effect Toxicity 0.000 description 1
125000004205 trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1
238000002424 x-ray crystallography Methods 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/72—Nitrogen atoms
- C07D213/74—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/52—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings condensed with carbocyclic rings or ring systems
- C07D263/54—Benzoxazoles; Hydrogenated benzoxazoles
- C07D263/58—Benzoxazoles; Hydrogenated benzoxazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Animal Behavior & Ethology (AREA)
Veterinary Medicine (AREA)
Diabetes (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Life Sciences & Earth Sciences (AREA)
Public Health (AREA)
General Health & Medical Sciences (AREA)
Hematology (AREA)
Obesity (AREA)
Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Emergency Medicine (AREA)
Endocrinology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Plural Heterocyclic Compounds (AREA)
Pyridine Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

CA002139442A 1992-07-03 1993-06-29 Heterocyclic compounds as pharmaceutical Abandoned CA2139442A1 (en)

Applications Claiming Priority (6)

Application Number	Priority Date	Filing Date	Title
GB929214185A GB9214185D0 (en)	1992-07-03	1992-07-03	Novel compounds
GB9214185.2		1992-07-03
GB9227030.5		1992-12-29
GB929227030A GB9227030D0 (en)	1992-12-29	1992-12-29	Novel compounds
GB939311027A GB9311027D0 (en)	1993-05-28	1993-05-28	Novel compounds
GB9311027.8		1993-05-28

Publications (1)

Publication Number	Publication Date
CA2139442A1 true CA2139442A1 (en)	1994-01-20

Family

ID=27266276

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA002139442A Abandoned CA2139442A1 (en)	1992-07-03	1993-06-29	Heterocyclic compounds as pharmaceutical

Country Status (19)

Country	Link
US (2)	US6048883A (pl)
EP (2)	EP1000938A1 (pl)
JP (1)	JPH07508747A (pl)
KR (1)	KR950702545A (pl)
CN (2)	CN1042532C (pl)
AT (1)	ATE207470T1 (pl)
AU (1)	AU678974B2 (pl)
CA (1)	CA2139442A1 (pl)
CZ (1)	CZ1095A3 (pl)
DE (1)	DE69331010D1 (pl)
FI (1)	FI950016A7 (pl)
HU (1)	HUT71247A (pl)
MX (1)	MX9303981A (pl)
NO (2)	NO305318B1 (pl)
NZ (1)	NZ253742A (pl)
PL (2)	PL174610B1 (pl)
RU (1)	RU2134686C1 (pl)
SK (1)	SK695A3 (pl)
WO (1)	WO1994001420A1 (pl)

Families Citing this family (78)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB9311661D0 (en) *	1993-06-05	1993-07-21	Smithkline Beecham Plc	Novel compounds
GB9311644D0 (en) *	1993-06-05	1993-07-21	Smithkline Beecham Plc	Novel compounds
GB9315148D0 (en) *	1993-07-22	1993-09-08	Smithkline Beecham Plc	Novel compounds
GB9326171D0 (en) *	1993-12-22	1994-02-23	Smithkline Beecham Plc	Novel compounds
WO1996004261A1 (en) *	1994-07-29	1996-02-15	Smithkline Beecham Plc	Benzoxazoles and pryridine derivatives useful in the treatment of the type ii diabetes
TR199500916A2 (tr) *	1994-07-29	1996-06-21	Smithkline Beecham Plc	Tipta kullanilmak üzere yeni bilesikler.
GB9600464D0 (en) *	1996-01-09	1996-03-13	Smithkline Beecham Plc	Novel method
US6090836A (en) *	1996-02-02	2000-07-18	Merck & Co., Inc.	Benzisoxazole-derived antidiabetic compounds
US5847008A (en) *	1996-02-02	1998-12-08	Merck & Co., Inc.	Method of treating diabetes and related disease states
US5859051A (en) *	1996-02-02	1999-01-12	Merck & Co., Inc.	Antidiabetic agents
US6020382A (en) *	1996-02-02	2000-02-01	Merck & Co., Inc.	Method of treating diabetes and related disease states
GB9604242D0 (en)	1996-02-28	1996-05-01	Glaxo Wellcome Inc	Chemical compounds
US6204277B1 (en) *	1996-08-19	2001-03-20	Japan Tobacco Inc.	Propionic acid derivatives and applications thereof
US6160000A (en) *	1996-12-23	2000-12-12	Merck & Co., Inc.	Antidiabetic agents based on aryl and heteroarylacetic acids
US6090839A (en) *	1996-12-23	2000-07-18	Merck & Co., Inc.	Antidiabetic agents
KR20070011651A (ko)	1997-06-18	2007-01-24	스미스클라인비이참피이엘시이	티아졸리딘디온 및 술포닐우레아를 사용한 당뇨병의 치료
US6444816B1 (en)	1997-10-27	2002-09-03	Dr. Reddy's Research Foundation	Fused 7-oxo-pyrimidinyl compounds, preparation, composition and use thereof
US6265401B1 (en)	1997-10-27	2001-07-24	Reddy-Cheminor, Inc.	Bicyclic compounds and their use in medicine, process for their preparation and pharmaceutical compositions containing them
WO1999019313A1 (en) *	1997-10-27	1999-04-22	Dr. Reddy's Research Foundation	Novel tricyclic compounds and their use in medicine; process for their preparation and pharmaceutical compositions containing them
GB2380997B (en) *	1997-10-27	2003-07-02	Reddys Lab Ltd Dr	Novel aryl-oxysubstituted alkyl carboxylic acids; process for their preparation and pharmaceutical compositions containing them
AU752059B2 (en)	1997-10-27	2002-09-05	Dr. Reddy's Laboratories Limited	Bicyclic compounds, process for their preparation and pharmaceutical compositions containing them
AU749505B2 (en) *	1997-10-27	2002-06-27	Dr. Reddy's Laboratories Limited	Novel tricyclic compounds and their use in medicine; process for their preparation and pharmaceutical compositions containing them
US6369067B1 (en)	1997-10-27	2002-04-09	Dr. Reddy's Research Foundation	Monocyclic compounds and their use in medicine: process for their preparation and pharmaceutical compositions containing them
CN1280574A (zh)	1997-10-27	2001-01-17	雷迪研究基金会	新的杂环化合物及其在医药中的应用、它们的制备方法和含有它们的药物组合物
US6440961B1 (en)	1997-10-27	2002-08-27	Dr. Reddy's Research Foundation	Tricyclic compounds and their use in medicine: process for their preparation and pharmaceutical compositions containing them
ATE286032T1 (de) *	1998-04-23	2005-01-15	Reddys Lab Ltd Dr	Heterozyklische verbindungen,und deren verwendung in arzneimittel,verfahren zu deren herstellung und diese enthaltende pharmazeutische zusammenstellungen
SE9801992D0 (sv) *	1998-06-04	1998-06-04	Astra Ab	New 3-aryl-2-hydroxypropionic acid derivative I
AR023700A1 (es)	1998-11-12	2002-09-04	Smithkline Beecham Plc	Un procedimiento para preparar una composicion farmaceutica que comprende un sensibilizador de insulina
HK1040910B (en)	1998-11-12	2009-06-26	Smithkline Beecham Plc	Pharmaceutical composition for modified release of an insulin sensitiser and metformin
US7000106B2 (en) *	1999-03-26	2006-02-14	Siemens Communications, Inc.	Methods and apparatus for kernel mode encryption of computer telephony
US6972294B1 (en)	1999-04-20	2005-12-06	Novo Nordisk, A/S	Compounds, their preparation and use
DE60005973T2 (de)	1999-08-27	2004-05-13	Eli Lilly And Co., Indianapolis	Biaryl-oxa(thia)zolderivate und ihre verwendung als ppars modulatoren
SE9904415D0 (sv) *	1999-12-03	1999-12-03	Astra Ab	New process
ES2449194T3 (es) *	2000-01-19	2014-03-18	Cadila Healthcare Limited	Compuestos que tienen actividades hipolipidémica e hipocolesterolémica, procedimiento para su preparación y composiciones farmacéuticas que los contienen
US6555577B1 (en)	2000-01-28	2003-04-29	Novo Nordisk A/S	Compounds, their preparation and use
BR0107902A (pt) *	2000-01-28	2002-11-05	Novo Nordisk As	Composto, composição farmacêutica, métodos para o tratamento de doenças, e para o tratamento e/ou prevençao de, condições mediadas por receptores nucleares, e diabetes e/ou obesidade, uso de uim composto, processo para a preparação de um composto, e, método para tratar diabetes de tipo i, diabetes de tipo ii, tolerância prejudicada à glucose, resistência à insolina ou obesidade
US6569901B2 (en)	2000-01-28	2003-05-27	Novo Nordisk A/S	Alkynyl-substituted propionic acid derivatives, their preparation and use
US6509374B2 (en)	2000-04-17	2003-01-21	Novo Nordisk A/S	Compounds, their preparation and use
GB0014969D0 (en)	2000-06-19	2000-08-09	Smithkline Beecham Plc	Novel method of treatment
US6559335B2 (en)	2000-09-22	2003-05-06	Dr. Reddy's Laboratories Limited	Process for the preparation of 3-aryl-2-hydroxy propanoic acid
TWI311133B (en) *	2001-04-20	2009-06-21	Eisai R&D Man Co Ltd	Carboxylic acid derivativeand the salt thereof
AU2002342244B2 (en)	2001-05-15	2005-06-16	F. Hoffmann-La Roche Ag	Carboxylic acid substituted oxazole derivatives for use as PPAR-alpha and -gamma activators in the treatment of diabetes
US6987123B2 (en)	2001-07-26	2006-01-17	Cadila Healthcare Limited	Heterocyclic compounds, their preparation, pharmaceutical compositions containing them and their use in medicine
US7067530B2 (en)	2001-07-30	2006-06-27	Novo Nordisk A/S	Compounds, their preparation and use
US6869967B2 (en)	2001-07-30	2005-03-22	Novo Nordisk A/S	Peroxisome proliferator-activated receptor (PPAR) active vinyl carboxylic acid derivatives
WO2003016265A1 (en)	2001-08-17	2003-02-27	Eisai Co., Ltd.	Cyclic compound and ppar agonist
US7220877B2 (en)	2001-10-17	2007-05-22	Novo Nordisk A/S	Compounds, their preparation and use
JP2005518408A (ja)	2001-12-29	2005-06-23	ノボ　ノルディスク　アクティーゼルスカブ	異常脂肪血症を治療するための、ｇｌｐ−１化合物と他の薬物との組み合わせ使用
RU2228753C2 (ru) *	2002-01-31	2004-05-20	Пермская государственная фармацевтическая академия	Изоникотиноилгидразид фталевой кислоты, проявляющий гипогликемическую активность
US8268352B2 (en) *	2002-08-05	2012-09-18	Torrent Pharmaceuticals Limited	Modified release composition for highly soluble drugs
US8216609B2 (en) *	2002-08-05	2012-07-10	Torrent Pharmaceuticals Limited	Modified release composition of highly soluble drugs
US7232828B2 (en) *	2002-08-10	2007-06-19	Bethesda Pharmaceuticals, Inc.	PPAR Ligands that do not cause fluid retention, edema or congestive heart failure
ES2350340T3 (es) *	2002-08-30	2011-01-21	F. Hoffmann-La Roche Ag	Nuevos compuestos de 2-aril-tiazol como agonistas de pparalfa y ppargamma.
NZ537979A (en)	2002-09-12	2007-08-31	Hoffmann La Roche	N-substituted-1H-indol-5-propionic acid compounds as PPAR agonists useful for the treatment of diabetes
ATE405560T1 (de)	2002-11-25	2008-09-15	Hoffmann La Roche	Indolderivaten
US7816385B2 (en)	2002-12-20	2010-10-19	High Point Pharmaceuticals, Llc	Dimeric dicarboxylic acid derivatives, their preparation and use
US6653334B1 (en)	2002-12-27	2003-11-25	Kowa Co., Ltd.	Benzoxazole compound and pharmaceutical composition containing the same
US20040248972A1 (en) *	2003-05-16	2004-12-09	Ambit Biosciences Corporation	Compounds and uses thereof
US20040242673A1 (en) *	2003-05-16	2004-12-02	Ambit Biosciences Corporation	Heterocyclic compounds and uses thereof
US20050182125A1 (en) *	2003-05-16	2005-08-18	Ambit Biosciences Corporation	Pyrrole compounds and uses thereof
PL371841A1 (pl) *	2004-12-20	2006-06-26	ADAMED Sp.z o.o.	Nowe związki pochodne kwasu 3-fenylopropionowego
CA2598934A1 (en) *	2005-02-25	2006-08-31	Takeda Pharmaceutical Company Limited	Pyridyl acetic acid compounds
WO2008117982A1 (en) *	2007-03-28	2008-10-02	Crystal Genomics, Inc.	Heterocyclic carboxylic acid derivatives and pharmaceutical composition for inhibiting lipid accumulation containing same
US20100274022A1 (en) *	2007-04-26	2010-10-28	Pharmafrontier Co., Ltd.	G protein-coupled receptor inhibitor and pharmaceutical product
RU2429728C1 (ru) *	2010-03-09	2011-09-27	Государственное образовательное учреждение высшего профессионального образования Воронежская государственная технологическая академия (ГОУ ВПО ВГТА)	Сухая белково-растительная смесь для производства кислородного коктейля
EP3009136A1 (en)	2011-01-31	2016-04-20	Cadila Healthcare Limited	Treatment for lipodystrophy
IN2013MU01468A (pl)	2013-04-22	2015-04-17	Cadila Healthcare Ltd
PH12015502667B1 (en)	2013-05-30	2023-10-18	Zydus Lifesciences Ltd	A process for preparation of pyrroles having hypolipidemic hypocholesteremic activities
TW201636015A (zh)	2013-07-05	2016-10-16	卡地拉保健有限公司	協同性組成物
IN2013MU02470A (pl)	2013-07-25	2015-06-26	Cadila Healthcare Ltd
CN103467407B (zh) *	2013-09-03	2015-04-22	浙江医药高等专科学校	四氮唑羧酸类化合物及其用途
CN103467405B (zh) *	2013-09-03	2015-01-07	浙江医药高等专科学校	一类四氮唑羧酸类化合物、其制备方法和用途
CN103467409B (zh) *	2013-09-03	2015-01-07	浙江医药高等专科学校	取代的四氮唑羧酸类化合物及其用途
CN103467406B (zh) *	2013-09-03	2014-12-17	浙江医药高等专科学校	卤素取代的四氮唑羧酸类化合物、其制备方法和用途
CN103467408B (zh) *	2013-09-03	2015-01-21	浙江医药高等专科学校	一类四氮唑羧酸类化合物及其用途
IN2013MU02905A (pl)	2013-09-06	2015-07-03	Cadila Healthcare Ltd
WO2017064635A2 (en)	2015-10-14	2017-04-20	Cadila Healthcare Limited	Pyrrole compound, compositions and process for preparation thereof
BR112019011740A2 (pt)	2016-12-09	2019-10-29	Cadila Healthcare Limited	composição farmacêutica e método para o tratamento de colangite biliar primária

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
SG59988A1 (en) *	1987-09-04	1999-02-22	Beecham Group Plc	Substituted thiazolidinedione derivatives
US5232925A (en) *	1987-09-04	1993-08-03	Beecham Group P.L.C.	Compounds
US5194443A (en) *	1987-09-04	1993-03-16	Beecham Group P.L.C.	Compounds
WO1989008650A1 (en) *	1988-03-08	1989-09-21	Pfizer Inc.	Thiazolidinedione hypoglycemic agents
US5089514A (en) *	1990-06-14	1992-02-18	Pfizer Inc.	3-coxazolyl [phenyl, chromanyl or benzofuranyl]-2-hydroxypropionic acid derivatives and analogs as hypoglycemic agents
GB9017218D0 (en) *	1990-08-06	1990-09-19	Beecham Group Plc	Novel compounds

1993
- 1993-06-29 CA CA002139442A patent/CA2139442A1/en not_active Abandoned
- 1993-06-29 PL PL93307087A patent/PL174610B1/pl unknown
- 1993-06-29 HU HU9500006A patent/HUT71247A/hu unknown
- 1993-06-29 SK SK6-95A patent/SK695A3/sk unknown
- 1993-06-29 AU AU45068/93A patent/AU678974B2/en not_active Ceased
- 1993-06-29 EP EP99204395A patent/EP1000938A1/en not_active Withdrawn
- 1993-06-29 EP EP93914841A patent/EP0648212B1/en not_active Expired - Lifetime
- 1993-06-29 RU RU94046169A patent/RU2134686C1/ru active
- 1993-06-29 KR KR1019940704886A patent/KR950702545A/ko not_active Ceased
- 1993-06-29 AT AT93914841T patent/ATE207470T1/de not_active IP Right Cessation
- 1993-06-29 CZ CZ9510A patent/CZ1095A3/cs unknown
- 1993-06-29 JP JP6503071A patent/JPH07508747A/ja active Pending
- 1993-06-29 PL PL93316129A patent/PL176885B1/pl unknown
- 1993-06-29 DE DE69331010T patent/DE69331010D1/de not_active Expired - Lifetime
- 1993-06-29 NZ NZ253742A patent/NZ253742A/en unknown
- 1993-06-29 WO PCT/GB1993/001363 patent/WO1994001420A1/en not_active Ceased
- 1993-06-29 US US08/360,755 patent/US6048883A/en not_active Expired - Fee Related
- 1993-07-01 MX MX9303981A patent/MX9303981A/es not_active IP Right Cessation
- 1993-07-02 CN CN93109874A patent/CN1042532C/zh not_active Expired - Fee Related
1995
- 1995-01-02 NO NO950009A patent/NO305318B1/no not_active IP Right Cessation
- 1995-01-02 FI FI950016A patent/FI950016A7/fi unknown
- 1995-06-02 US US08/458,335 patent/US5869495A/en not_active Expired - Fee Related
1998
- 1998-05-14 CN CN98108909A patent/CN1215724A/zh active Pending
1999
- 1999-01-19 NO NO990227A patent/NO990227D0/no unknown

Also Published As

Publication number	Publication date
NO990227L (no)	1995-03-02
DE69331010D1 (de)	2001-11-29
FI950016A0 (fi)	1995-01-02
US6048883A (en)	2000-04-11
KR950702545A (ko)	1995-07-29
EP0648212B1 (en)	2001-10-24
NO950009L (no)	1995-03-02
SK695A3 (en)	1995-07-11
AU678974B2 (en)	1997-06-19
EP0648212A1 (en)	1995-04-19
CN1095716A (zh)	1994-11-30
EP1000938A1 (en)	2000-05-17
RU2134686C1 (ru)	1999-08-20
HU9500006D0 (en)	1995-03-28
CN1042532C (zh)	1999-03-17
CN1215724A (zh)	1999-05-05
NO990227D0 (no)	1999-01-19
WO1994001420A1 (en)	1994-01-20
PL307087A1 (en)	1995-05-02
JPH07508747A (ja)	1995-09-28
US5869495A (en)	1999-02-09
NZ253742A (en)	1997-06-24
RU94046169A (ru)	1996-10-27
AU4506893A (en)	1994-01-31
NO950009D0 (no)	1995-01-02
HUT71247A (en)	1995-11-28
PL176885B1 (pl)	1999-08-31
ATE207470T1 (de)	2001-11-15
CZ1095A3 (en)	1995-10-18
PL174610B1 (pl)	1998-08-31
MX9303981A (es)	1994-04-29
NO305318B1 (no)	1999-05-10
FI950016A7 (fi)	1995-03-02

Legal Events

Date	Code	Title	Description
2000-01-06	EEER	Examination request
2003-06-30	FZDE	Discontinued

Publication	Publication Date	Title
CA2139442A1 (en)	1994-01-20	Heterocyclic compounds as pharmaceutical
WO1995017394A1 (en)	1995-06-29	Heterocyclic derivatives and their use in pharmaceuticals
JP6641367B2 (ja)	2020-02-05	ソマトスタチン受容体サブタイプ４（ｓｓｔｒ４）アゴニストとしてのモルホリンおよび１，４−オキサゼパンアミド
AU733316B2 (en)	2001-05-10	Pyrazolopyridylpyridazinone derivatives and process for preparing the same
US20120178750A1 (en)	2012-07-12	Niacin Receptor Agonists, Compositions Containing Such Compounds and Methods of Treatment
US20060040933A1 (en)	2006-02-23	Nonsteroidal antiinflammatory agents
US5952509A (en)	1999-09-14	Production of benzaldehyde compounds
CA2339773A1 (en)	2000-02-17	Substituted oxazoles and thiazoles derivatives as hppar gamma and hppar alpha activators
EP3573960B1 (en)	2023-08-16	N-{[2-(piperidin-1-yl)phenyl](phenyl)methyl}-2-(3-oxo-3,4-dihydro-2h-1,4-benzoxazin-7-yl)acetamide derivatives and related compounds as ror-gamma modulators for treating autoimmune diseases
EP1983994A2 (en)	2008-10-29	Oxazole ketones as modulators of fatty acid amide hydrolase
RU2261250C2 (ru)	2005-09-27	Соединения пиперазина и пиперидина
BG61728B1 (bg)	1998-04-30	2,9-дизаместени пурин-6-они
CN100415727C (zh)	2008-09-03	手性的噁唑-芳基丙酸衍生物和它们作为ppar激动剂的应用
JP2008308496A (ja)	2008-12-25	医薬
US8268817B2 (en)	2012-09-18	Substituted oxazole ketone modulators of fatty acid amide hydrolase
ES2544086T3 (es)	2015-08-27	Derivados de 2-metoxi-piridin-4-ilo
CZ281213B6 (cs)	1996-07-17	Způsob výroby oxoftalazinyloctových kyselin a jejich analogů
US20090042926A1 (en)	2009-02-12	Niacin Receptor Agonists, Compositions Containing Such Compounds and Methods of Treatment
SK12895A3 (en)	1995-08-09	3-(2-aminoethyl)-4-(3-trifluoromethyl-benzoyl)-3,4-dihydro-2h- -1,4-benzoxazine derivatives, method of their preparation and pharmaceutical composition containing of these derivatives
US5827865A (en)	1998-10-27	Heterocyclic compounds as pharmaceutical
JP3256841B2 (ja)	2002-02-18	ベンズアルデヒド化合物の製造法
JP4077054B2 (ja)	2008-04-16	ベンゾチアゾール及びベンゾオキサゾール誘導体の製法
HK1028600A (en)	2001-02-23	Heterocyclic compounds as pharmaceuticals
KR100599070B1 (ko)	2006-07-12	옥사졸 유도체의 제조 방법
KR20090077091A (ko)	2009-07-15	신규 퍼옥시좀 증식자-활성화 수용체 효능제인 화합물 및그 제조방법